adenylate cyclase inhibiting G protein-coupled glutamate receptor activity

Definition

Target type: molecularfunction

Combining with glutamate and transmitting the signal across the membrane by activating the alpha-subunit of an associated heterotrimeric G-protein complex to inhibit downstream adenylate cyclase activity. [GOC:bf, GOC:dph]

Adenylate cyclase inhibiting G protein-coupled glutamate receptors are a class of metabotropic glutamate receptors (mGluRs) that are characterized by their ability to inhibit the activity of adenylate cyclase, an enzyme that produces cyclic AMP (cAMP). These receptors are coupled to inhibitory G proteins, specifically Gi/o proteins, which upon activation, inhibit adenylate cyclase and consequently reduce intracellular cAMP levels. The mechanism of action involves the following steps:

1. **Ligand Binding:** Glutamate, the primary excitatory neurotransmitter in the brain, binds to the extracellular domain of the receptor.
2. **Conformational Change:** Glutamate binding triggers a conformational change in the receptor protein, activating its intracellular domain.
3. **G Protein Coupling:** The activated receptor interacts with and activates a G protein, specifically a Gi/o protein.
4. **Adenylate Cyclase Inhibition:** The activated Gi/o protein binds to and inhibits adenylate cyclase, reducing its activity.
5. **cAMP Reduction:** Consequently, the intracellular concentration of cAMP decreases.

The reduction in cAMP levels has various downstream effects, depending on the specific cell type and signaling pathways involved. In general, the inhibition of adenylate cyclase can lead to:

* **Reduced protein kinase A (PKA) activity:** cAMP is a key activator of PKA, so reduced cAMP levels result in decreased PKA activity.
* **Modulation of ion channel activity:** cAMP influences the activity of certain ion channels, and its reduction can alter their function.
* **Changes in gene expression:** cAMP can regulate gene transcription, and its decrease can affect the expression of specific genes.

The precise physiological roles of adenylate cyclase inhibiting G protein-coupled glutamate receptors vary depending on their specific subtype and location in the brain. However, they are known to play important roles in processes such as:

* **Synaptic plasticity:** They can modulate synaptic transmission and contribute to long-term potentiation (LTP) and long-term depression (LTD).
* **Neuroprotection:** They may protect neurons from excitotoxicity and other forms of damage.
* **Anxiety and depression:** They are implicated in the regulation of mood and emotional states.

In summary, adenylate cyclase inhibiting G protein-coupled glutamate receptors are important modulators of neuronal signaling, contributing to various physiological processes in the brain.'
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Proteins (5)

Compounds (89)